Monophasic and Biphasic Hyaluronic Acid Fillers for Esthetic Correction of Nasolabial Folds: A Meta-Analysis of Randomized Controlled Trials.

[BACKGROUND] Hyaluronic acid (HA) fillers have become the most popular dermal fillers for esthetic nasolabial folds (NLFs) correction. Based on the cross-linking method, they can be classified as monophasic or biphasic types.

[OBJECTIVES] The aim of this meta-analysis is to compare the efficacy and safety of monophasic HA fillers with that of biphasic HA fillers for treatment of NLFs. PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese databases were searched from inception to January 2021.

[METHODS] Randomized controlled trials (RCTs) that compared treatment outcomes of a monophasic HA filler with a biphasic HA filler for esthetic NLF correction were selected. Twenty-two RCTs with totally 1848 subjects were included to this meta-analysis. A significantly higher improvement of NLF severity score was seen for monophasic fillers than biphasic fillers at 2 (p = 0.005), 8 (p <0.0001), 12 (p = 0.03), 16 (p = 0.005), 24 (p <0.00001), 36 (p = 0.007), and 52 week (p <0.0001) after treatment.

[RESULTS] The effect was retained regardless of ethnicity, total injection volume, and baseline NLF severity. More subjects preferred monophasic fillers over biphasic ones (≤7 months: RR = 3.45, 95% CI 1.17 to 10.11; >7 months: RR = 2.37, 95% CI 1.45 to 3.86). Rate of post-injection pain was significantly lower for monophasic fillers (RR = 0.85, 95% CI 0.78 to 0.92, p <0.0001), but no statistical difference was observed for other post-injection adverse events. Compared to biphasic HA fillers, monophasic HA fillers were associated with a greater and more durable esthetic NLFs improvement, a lower rate of post-injection pain, and were favored by more patients.

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